Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.6.4.4 (kinesin)
 5,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cardiovascular benefits of statins, including atorvastatin (ATV), have been reported to be gender-dependent, but the underlying mechanism is unclear. In this study we examine whether estrogen and its metabolite, 2-methoxyestradiol (2ME), affect the rounding response of human vascular smooth muscle cells (SMCs) induced by ATV. Twenty-four hour treatment with ATV (10-100 microM) induced rounding of cultured human SMCs. Addition of 2ME (1-20 microM), but not 17beta-estradiol, for 2 h induced re-spreading of rounded cells. Our further studies showed that the effects of 2ME were mimicked by microtubule-disrupting drugs and inhibited by taxol. Inhibition of RhoA and ROCK (Rho-kinase) by C3-toxin and H-1152, respectively, blocked 2ME effects. 2ME effects were also blocked by treatment with either actin-interfering drugs, such as cytochalasin D and jasplakinolide, or myosin inhibitor blebbistatin. ML-7 and -9, the inhibitors for myosin light chain kinase, inhibited 2ME effect as well. ATV treatment induced a decrease of F-actin content and Thr18/Ser19 dual phosphorylation of myosin regulatory light chain (MRLC), which was rescued by 2ME or mevalonate. The rescue effects of 2ME on F-actin content and MRLC dual phosphorylation were abolished by taxol or H-1152. In addition, kinesin Eg5 inhibitor monastrol and dynein inhibitor erythro-9-3-(2-hydroxynonyl) adenine (EHNA) significantly blocked 2ME effects. Finally, our results revealed that 2ME inhibited the migration of SMCs induced by ATV (0.1 microM) in wound healing assay and Boyden chamber assay. In summary, our data show that 2ME, but not estrogen, inhibits ATV-induced rounding of human SMCs through induction of microtubule disassembly and activation of the Rho-ROCK-actinomyosin pathway.
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PMID:2-methoxyestradiol inhibits atorvastatin-induced rounding of human vascular smooth muscle cells. 1993 28

Cytokinesis is last but not least in cell division as it completes the formation of the two cells. The main role in cell plate orientation and expansion have been assigned to microtubules and kinesin proteins. However, recently we reported severe cytokinesis defect in BY-2 cells not accompanied by changes in microtubules dynamics. Here we also confirmed that distribution of kinesin NACK1 is not the cause of cytokinesis defect. We further explored inhibition of the cell plate expansion by ATP-competitive inhibitors. Two different inhibitors, 5-Iodotubercidin and ML-7 resulted in a very similar phenotype, which indicates that they target same protein cascade. Interestingly, in our previous study we showed that 5-Iodotubercidin treatment affects concentration of actin filaments on the cell plate, while ML-7 is inhibitor of myosin light chain kinase. Although not directly, it indicates importance of actomyosin complex in plant cytokinesis.
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PMID:Cytokinesis defect in BY-2 cells caused by ATP-competitive kinase inhibitors. 2766 76